Genetic Variant PLEKHA7:p.Ser1063Ser (chr11-16789264-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001329630.2(PLEKHA7):c.3189A>C(p.Ser1063Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,628 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 3 hom., cov: 33)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

PLEKHA7
NM_001329630.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.222

Publications

0 publications found

Variant links:

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013082981).

BP6

Variant 11-16789264-T-G is Benign according to our data. Variant chr11-16789264-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3037586.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.222 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHA7	NM_001329630.2	MANE Select	c.3189A>C	p.Ser1063Ser	synonymous	Exon 23 of 27	NP_001316559.1	E9PKC0
PLEKHA7	NM_001410960.1		c.3192A>C	p.Ser1064Ser	synonymous	Exon 23 of 27	NP_001397889.1	A0A8V8TMS3
PLEKHA7	NM_001329631.2		c.3192A>C	p.Ser1064Ser	synonymous	Exon 23 of 23	NP_001316560.1	Q6IQ23-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHA7	ENST00000531066.6	TSL:5 MANE Select	c.3189A>C	p.Ser1063Ser	synonymous	Exon 23 of 27	ENSP00000435389.1	E9PKC0
PLEKHA7	ENST00000355661.7	TSL:1	c.3189A>C	p.Ser1063Ser	synonymous	Exon 23 of 23	ENSP00000347883.2	Q6IQ23-1
PLEKHA7	ENST00000530489.5	TSL:1	c.2082A>C	p.Ser694Ser	synonymous	Exon 14 of 14	ENSP00000433467.1	H0YDE2

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000253

AC:

AN:

248628

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461344

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.00332

AC:

111

AN:

33480

American (AMR)

AF:

0.000201

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52900

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112004

Other (OTH)

AF:

0.000248

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000946

AC:

144

AN:

152284

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00296

AC:

123

AN:

41560

American (AMR)

AF:

0.000719

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000585

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000280

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PLEKHA7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.9

(source)

DANN

Benign

0.91

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.61

M_CAP

Benign

0.0034

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.99

PhyloP100

0.22

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.54

Vest4

0.27

MVP

0.25

ClinPred

0.070

GERP RS

-1.9

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over